Heart failure with sleep disordered breathing Circulatory System Heart failure
Conditions
Interventions
Intervention: Adaptive servo-ventilation.
The clinical study plan provides direct clinical visits of every patient at study entry, after 2 weeks, after 3 and 12 months, thereafter eve
Sponsors
ResMed Ltd (Sydney, Australia)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 14/08/2012: 1. At least 18 years old 2. Chronic heart failure (at least 12 weeks since diagnosis) according to the current applicable guidelines (European Society of Cardiology [ESC], American College of Cardiology [ACC]/American Heart Association [AHA]) 3. Left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] less or equal than 45% by imaging method such as echocardiography, radionuclide (March, 6th 2009) 4. NYHA class III or IV at the time of inclusion or NYHA class II with at least one hospitalisation for HF in the last 24 months (March, 6th 2009) 5. No hospitalisation for HF for at least 4 weeks prior to inclusion 6. Optimised medical treatment according to applicable guidelines with no new class of disease modifying drug for more than 4 weeks prior to randomisation. In case of no beta blockers or angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) antagonists the reasons must be documented 7. SDB (Apnoea-Hypopnoea Index [AHI] greater than 15/hour with greater than or equal to 50% central events and a central AHI greater than or equal to 10 hours, derived from polygraphy or polysomnography (based on total recording time [TRT]), documented less than 4 weeks before randomisation. Flow measurement has to be performed with nasal cannula 8. Patient is able to fully understand study information and signed informed consent Previous inclusion criteria until 14/08/2012: 1. At least 18 years old 2. Chronic heart failure (at least 12 weeks since diagnosis) according to the current applicable guidelines (European Society of Cardiology [ESC], American College of Cardiology [ACC]/American Heart Association [AHA]) 3. Left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] less than 40% by imaging method such as echocardiography, radionuclide angiography, left ventriculography, or cardiac magnetic resonance imaging) documented less than 12 weeks before randomisation 4. New York Heart Association (NYHA) class III or IV at the time of inclusion or NYHA class II with at least one hospitalisation for heart failure (HF) in the last 12 months 5. No hospitalisation for HF for at least 4 weeks prior to inclusion 6. Optimised medical treatment according to applicable guidelines with no new class of disease modifying drug for more than 4 weeks prior to randomisation. In case of no beta blockers or angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) antagonists the reasons must be documented 7. SDB (Apnoea-Hypopnoea Index [AHI] greater than 15/hour with greater than or equal to 50% central events and a central AHI greater than or equal to 10 hours, derived from polygraphy or polysomnography (based on total recording time [TRT]), documented less than 4 weeks before randomisation. Flow measurement has to be performed with nasal cannula 8. Patient is able to fully understand study information and signed informed consent
Exclusion criteria
Exclusion criteria: 1. Significant chronic obstructive pulmonary disease (COPD) with forced expiratory volume within one second (FEV1) less than 50% (European Respiratory Society criteria) in the last four weeks before randomisation 2. Oxygen saturation at rest during the day less than or equal to 90% at inclusion 3. Current use of positive airway pressure (PAP) therapy 4. Life expectancy less than 1 year for diseases unrelated to chronic HF 5. Cardiac surgery, percutaneous coronary intervention (PCI), myocardial infarction (MI) or unstable angina within 6 months prior to randomisation 6. Cardiac resynchronisation therapy (CRT)-implantation or implanatable cardioverter-defibrillator (ICD)-implantation scheduled or within 6 months prior to randomisation 7. Transient ischaemic attack (TIA) or stroke within 3 months prior to randomisation 8. Primary haemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial 9. Acute myocarditis/pericarditis within 6 months prior to randomisation 10. Untreated or therapy refractory restless legs-syndrome (RLS) 11. Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 20/05/2015: The primary target parameters are defined as time to first event of: 1. All cause mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure 2. Cardiovascular mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure 3. All cause mortality or all cause hospitalisation/prolongation of hospitalisation The three combinations are not tested in parallel but in this hierarchical order: "Cardiovascular mortality" and "unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure" will be evaluated by the Endpoint Review Committee (ERC). Definition will be documented in rules of procedure of the ERC. Heart transplantation, appropriate shock from ICD, long term assist device (LTAD) insertion and survived resuscitation of sudden cardiac arrest are counted as cardiovascular death, survived resuscitation for other reasons is counted as all cause death. It is assumed, that the intervention reduces the hazard rate by 20% and that the event rate in the control group is 35% in the first year. It is also assumed that the hazard rate is constant over time. The primary target parameters will be measured at the final assessment. Previous primary outcome measures: The primary target parameters are defined as time to first event of: 1. All cause mortality or unplanned hospitalisation for worsening heart failure 2. Cardiovascular mortality or unplanned hospitalisation for worsening heart failure 3. All cause mortality or all cause hospitalisation The three combinations are not tested in parallel but in this hierarchical order: "Cardiovascular mortality" and "unplanned hospitalisation for worseni | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 20/05/2015: 1. Time until death 2. Time until non cardiovascular death 3. Time until cardiovascular death 4. Time until unplanned hospitalisation/prolongation of hospitalisation due to worsening of heart failure or cardiovascular death 5. Time until unplanned hospitalisation/prolongation of hospitalisation for other reasons or death 6. Time until unplanned hospitalisation/prolongation of hospitalisation for cardiovascular cause or cardiovascular death 7. Time to first adequate shock in patients with ICD (evaluation of appropriateness will also be made by the ERC), LTAD insertion or cardiovascular death 8. Time to first survived resuscitation for any reason (evaluation will also be made by the ERC) 9. Time to first survived resuscitation of sudden cardiac arrest (evaluation will also be made by the ERC) 10. Percent of follow up days which patient survives and is not hospitalised /hospital stay is not prolonged for cardiovascular cause 11. Percent of follow up days which patient survives and is not hospitalised /hospital stay is not prolonged for other reasons 12. Changes in NYHA classification as compared to baseline 13. Changes in Quality of Life (QoL) (Minnesota) as compared to baseline 14. Changes in renal function (based on serum creatinine) as compared to baseline 15. Changes in Six Minute Walking Distance (6MWD) as compared to baseline 16. Number and cost of hospitalisations (with tariff/Diagnosis-Related Groups [DRG], diagnoses and procedures for calculating DRG or length of stay and level of care provided) 17. Difference in utilities/QoL (Minnesota and EQ5D) compared to control arm 18. Difference in cost of resources consumed | — |
Countries
Australia, Czech Republic, Denmark, Finland, France, Germany, Netherlands, Norway, Sweden, Switzerland, United Kingdom
Outcome results
None listed